Neoadjuvant Nivolumab Yields High Response in Newly Diagnosed NSCLC

Neoadjuvant treatment with the anti–programmed death 1 (PD-1) antibody nivolumab was safe and resulted in pathological responses in nearly half of a small cohort of patients with stage I –III non–small-cell lung cancer (NSCLC), according to results of a new trial.

“The rationale for neoadjuvant anti–PD-1 treatment of resectable NSCLC was essentially to use the primary tumor as a ‘vaccine’ to induce Tcells against the tumor antigens that would then circulate through the body systemically and seek out any distant sites of micrometastases,” said Drew Pardoll, MD, PhD, of the Johns Hopkins School of Medicine in Baltimore, according to a press release.

Micrometastases are the primary source of relapse after surgery.

Pardoll presented results of the study at the American Association for Cancer Research Annual Meeting, held April 14–18 in Chicago (Abstract CT079). The trial enrolled a total of 22 patients with newly diagnosed, resectable, stage I–III NSCLC; of those, 21 received nivolumab prior to resection, and 20 went on to undergo surgery.

Nine of the 20 patients (45%) demonstrated a major pathologic response, defined as 10% or fewer viable cancer cells detectable in the resected tumor. Pardoll said that 2 patients had no evidence of viable cells in the resected tumor sample.

“This is particularly striking given that surgery was done, in most cases, just 4 weeks after the first dose of anti–PD-1 treatment,” he said. “Our result of a 45% major pathologic response rate is very encouraging, considering prior studies showing that a major pathologic response after neoadjuvant chemotherapy in lung cancer is associated with long-term survival.”

The median time from the second of two nivolumab doses to surgery was 18 days. Pathologic responses were seen regardless of programmed death ligand 1 expression, but the responses were closely associated with tumor mutation burden. After a median follow-up of 12 months, 16 of the 20 patients were alive and had no recurrence of disease. At 18 months, the recurrence-free survival (RFS) rate was 73%, the median RFS had not yet been reached.

“While it's still too early to tell whether our findings will translate into lower relapse rate and improved survival, pending confirmation in a larger study, we are very optimistic that this approach will eventually be practice-changing and may augment or even replace chemotherapy prior to surgical resection,” Pardoll said. A co-principal investigator, Patrick Forde, MBBCh, also of Johns Hopkins, noted that the small sample size does limit interpretation of this study, but he agreed that the results are highly encouraging.

Pardoll noted that as many as 75 trials are ongoing involving neoadjuvant treatment with PD-1 blockade, across seven cancer types. The results of this study were published simultaneously in the New England Journal of Medicine.